Cytotoxic T lymphocytes (CTLs) have been shown to recognize epitope peptides derived from the tumor-associated antigens (TAAs) found on the major histocompatibility complex (MHC) class I molecule, and then kill the tumor cells. Since the discovery of the melanoma antigen (MAGE) family, many other TAAs have been discovered through immunological approaches (NPL1: Boon T, Int J Cancer 1993 May 8, 54(2):177-80; NPL2: Boon T & van der Bruggen P, J Exp Med 1996 Mar. 1, 183(3):725-9). Some of these TAAs are currently undergoing clinical development as immunotherapeutic targets.
In several of these TAAs, epitope peptides that can be recognized by CTLs are identified and their application in immunotherapy for various types of cancer is anticipated (NPL3: Harris C C, J Natl Cancer Inst 1996 Oct. 16, 88(20): 1442-55; NPL4: Butterfield L H et al., Cancer Res 1999 Jul. 1, 59(13): 3134-42; NPL5: Vissers J L et al., Cancer Res 1999 Nov. 1, 59(21): 5554-9; NPL6: van der Burg S H et al., J Immunol 1996 May 1, 156(9) 3308-14; NPL7: Tanaka F et al., Cancer Res 1997 Oct. 15, 57(20): 4465-8; NPL8: Fujie T et al., Int J Cancer 1999 Jan. 18, 80(2): 169-72; NPL9: Kikuchi M et al., Int J Cancer 1999 May 5, 81(3): 439-66; NPL10: Oiso M et al., Int J Cancer 1999 May 5, 81(3): 387-94). Until now, several clinical trials using these TAA-derived CTL epitope peptides have been reported. Unfortunately, many of these clinical trials show a low objective response rate (NPL11: Belli F et al., J Clin Oncol 2002 Oct. 15, 20(20): 4169-80; NPL12: Coulie P G et al., Immunol Rev 2002 October, 188: 33-42; NPL13: Rosenberg S A et al., Nat Med 2004 September, 10(9): 909-15). Therefore, there is still demand for identification of novel CTL epitopes that can be used in cancer immunotherapy.
CDCA1 (cell division cycle associated 1; also described as NUF2, NDC80 kinetochore complex component: Nuf2; reference sequence: GeneBank Accession Number NM_145697 (SEQ ID NO: 81) or GeneBank Accession Number NM_031423 (SEQ ID NO: 83)), has been identified as a member of the genes co-expressed with CDC2, cyclin, topoisomerase II and other cell cycle genes (NPL14: Walker et al., Curr Cancer Drug Targets 2001 May; 1(1): 73-83). CDCA1 has been found to be related to the centromere of HeLa cells undergoing mitotic division, and is considered to be a functional homologue of yeast Nuf2 (NPL15: Wigge P A et al., J Cell Biol 2001 Jan. 22; 152(2): 349-60). Meanwhile, CDCA1 has been identified as a gene up-regulated in non-small cell lung cancer by gene expression profile analysis using a genome-wide cDNA microarray containing 23,040 genes (NPL16: Hayama et al., Cancer Res 2006 Nov. 1; 66(21): 10339-48; PTL1: WO2007/013480; PTL2: WO2005/089735). The CDCA1 expression was up-regulated in both tumors and tumor cell lines, and was not detected in normal organs except the testis (NPL16; PTL1). Further, siRNA-mediated down-regulation of the CDCA1 expression caused suppression of cell proliferation in CDCA1-expressing lung cancer cell lines.
Recently, CDCA1-derived HLA-A2-restricted CTL epitope peptides (NPL17: Harao et al., Int J Cancer. 2008: 123(11): 2616-25; PTL3: WO2009/025117) and HLA-A24-restricted CTL epitope peptides (PTL4: WO2009/153992) have been identified. These peptides are effective in cancer patients having the HLA-A2 type or HLA-A24 type, but cannot be expected to have effect on cancer patients who do not have these HLA types.